Drugs in Hypertension yp yp yp yp

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Drugs in Hypertension

                                   Dr. Yuri Clement
                                Pharmacology Unit, FMS

 Revision of physiological control of BP.

 What is hypertension? Associated risks of uncontrolled hypertension


 1. Sympathetic Nervous System inhibition
       β-blockers, α1 blockers, mixed α, β blockers, central α agonists,
       peripheral adrenergic blockers.

2.   Sodium/Renin Angiotensin Aldosterone System balance
        Diuretics, ACE inhibitors, AT11 receptors blockers

3.   Vasodilators
        Ca2+-channel blockers, oral and parenteral vasodilators

Mechanisms of action, other indications, contraindications and adverse effects

            Hemodynamic factors affecting BP

    Arterial Blood            Cardiac Output   Total Peripheral
                   ≈                         x Resistance (TPR)
      Pressure                    (CO)

                                                         Arteriolar volume

                                  Heart rate                      Blood volume
                     Contractility           Filling pressure
                                                                  Venous tone

             BP Regulation:
             SNS and RAAS
Baroreceptor reflex system mediated
                             ↑β1 receptor                 ↑ CO
             th ti         cardiac activation
        activity                                                        ↑ BP
                             ↑α1 receptor                ↑ TPR
                       smooth muscle activation

       ↓ BP                          volume-
                         Renal blood volume-pressure system

     ↓ Renal flow                ↑ renin           ↑ Angiotensin II


         ↓GFR              ↑Na+, H2O retention      ↑ Blood volume

       What is hypertension?
  JNC 6 Category                                       JNC 7 Category (2004)
                              SBP/DBP (mmHg)

  Optimal                     <120/80                  NORMAL

  Normal                      120-129/80-
  Borderline                  130-139/85-

  Hypertension                >140/90                  HYPERTENSION

  Stage 1                     140-159/90-
                              140-159/90-99            STAGE 1

  Stage 2 (moderate)          160-179/100-
                                                       STAGE 2
  Stage 3 (severe)            ≥180/110

A chronic disease of persistent elevated arterial blood pressure.


       1o or essential hypertension (> 95%)
               Gender and age

       2o hypertension (~5%)
               Chronic renal disease
               Cushing’s syndrome and glucocorticoid excess states
               1o aldosteronism and other mineralocorticoid excess states
               Coarctation of the aorta

 Associated risks
      Chronic ↑arterial BP ↑ likelihood of morbidity
      and mortality.

      1.   CAD
      2.   LVH
      3.   CHF
      4.   MI
      5    Arrhythmias
      6.   Angina
      7.   Stroke
      8.   Dementia
      9.   Renal disease
CVD risk doubles for each increment of 20/10 mmHg

 Why treat?
                     Treating hypertension:
                      – ↓stroke by 40% - 45%
                      – ↓CHF by 40% - 50%
                      – ↓CAD by 16% - 25%

                     >30% unaware
                     Educational intervention ↓ BP.
                     In UK, only ~6% adequately treated.

               Drug classification
                                     SNS inhibition
           β antagonists            Mi d α,β antagonists
                                    Mixed      t    it            Central α2 agonists

                           α1 antagonists                Peripheral adrenergic

                               Sodium/RAAS balance
               Diuretics                ACE Inhibitors             ATII antagonists

           Ca2+ channel blockers                               Others

                                 β antagonists
Generic name Trade name(s)                  Doses available
Propranolol          Inderal®               Oral: 10, 20, 40, 60, 80, 90mg; 4, 8mg/mL oral
                                            soln; Inderal LA: 60, 80, 120, 160mg
                                            Parenteral: 1mg/mL soln
Nadolol              Corgard®               Oral: 20, 40, 80, 120, 160mg

Pindolol             Visken®                Oral: 5, 10mg

Acebutolol (*)       Sectral®               Oral: 200, 400mg

Metoprolol (*)       Toprol®,               Oral: 50, 100mg; XL: 25, 50, 100, 200mg
                     Lopressor®                           g
                                            Parenteral: 1mg/mL soln

Atenolol (*)         Tenormin®              Oral: 25, 50, 100mg;
                                            Parenteral: 0.5mg/mL soln
Betaxolol (*)        Kerlone®               Oral: 10, 20mg

Bisoprolol (*)       Zebeta®                Oral:5, 10mg

                                   (*) cardioselective

                  Mechanism of Action
       Acute effect                                           Long term effect
β1 blockade in myocardial cells                        β1 blockade in juxtaglomerular cells
                 -ve inotropic
                 -ve chronotropic
                                      ↓ aldosterone
            ↓ CO                                               ↓ Renin release
                                     ↓ Na+ retention

       Shift in whole body                                 ↓ [Angiotensin II]plasma
         autoregulation             ↓ Blood volume
                                                              ↓ arterial        g
                                                                            Change in arterial
                                                           vasoconstriction   remodelling

                                         ↓ TPR

                                           ↓ BP

               Other Indications

              Angina pectoris


              Glaucoma (applied topically)


              IHD and prevention of 2nd MI.

               Useful as monotherapy in Stage 1 HTN
            or with vasodilators (and diuretics) in stage 2.

  CHF and nodal conduction diseases.
     But,            (Coreg®)
   – But carvedilol (Coreg®), misoprolol and metoprolol
     ↓ mortality in CHF

  Non-selective β blockers in asthma. Cardio-selective
  Non-                                  Cardio-
  drugs lose selectivity at higher doses.

  Use with caution in insulin-dependent diabetic patients.
   – Glycogenolysis is adrenergically mediated. β
     blockers antagonize sympathetic response to
     hypoglycemia and blunt recovery.

Adverse Effects
CNS: Sedation, depression, lethargy, sleep disturbances

CV: CHF in LV dysfunction, heart block, bradyarrhythmias

Bronchospasms (non-selective blockers) in asthma and

↓HDL and ↑plasma triacylglycerol
       d l       ti l l        l

Abrupt cessation may induce unstable angina, MI or death in
patients predisposed to ischemic myocardial events. Taper
over 14 days.

                          α1 antagonists

Generic name Trade name(s)            Doses available
Prazosin          Minipress®          Oral: 1, 2, 5mg
Terazosin         Hytrin®             Oral: 1, 2, 5, 10mg
Doxazosin         Cardura®            Oral: 1, 2, 4, 8mg
Tamsulosin        Flomax®             Oral: 0.4mg

             α1 antagonists
            Mechanism of Action:
                Arterial and venous relaxation - ↓ TPR ; ↓ BP.
                Minimal ↑ CO, renal blood flow or GFR. No long-term tachycardia
                and ↑ renin release.

                 Benign prostatic hypertrophy and hypertension (prostate capsule
                 relaxation decreases resistance to urinary flow)

            Adverse Effects:
            1.  1st dose dizziness or syncope –give at bedtime (caution in elderly).
            2.                             (propranolol
                Initial reflex tachycardia (propranolol to counteract)
            3.  Postural hypotension
            4.  Infrequent and mild CNS: vivid dreams, lassitude and depression.

               Mixed α, β antagonists
Generic name        Trade name(s)    Doses available
Labetalol           Normodyne®       Oral:100, 200, 300mg
                                     Parenteral: 5mg/mL soln
Carvedilol          Coreg®           Oral: 3.125, 6.25, 12.5, 25mg

            Equimolar mixture of 4 stereoisomers:
            2 i ti 1 α1-bl k other non-selective β-bl k and
              inactive,      blocker, th non- l ti          blocker d
            β2- partial agonist.
            Useful in hypertensive emergencies (as iv)
            Similar efficacy and side-effects as β- and α1-antagonists
            when given orally.

            Mechanism of action:
    1.      α1 blockade and β2 stimulation cause rapid vasodilatation, ↓
            TPR leading to ↓BP

         Contraindications same as non-selective β blockers

  Peripheral adrenergic antagonists
Generic name         Trade name(s)     Doses available
Reserpine                    -         Oral: 0.1, 0.25mg
Guanethidine         Ismelin®          Oral: 10, 25mg
Guanadrel            Hylorel®          Oral: 10, 25mg

             Reserpine: Mechanism of action

       1.                             5-
               Binds avidly to NE and 5-HT storage vesicles in
                  t l d        i h l d        i
               central and peripheral adrenergic neurons
               inducing catecholamine leakage.

       2.      Overall Effect: Minimal active transmitter
               discharged from depolarized nerve endings.

       3.      Neurotransmitter depletion in brain and
               myocardium leads to sedation, depression and
            Rauwolfia serpentina root used in Ayuvedic medicine,
              isolated in 1950’s and used in Western medicine


            ↓CO, ↓TPR
            ↓HR (Na+ and H2O retention)
             HR, (N     d         t ti )
            Low doses + diuretic ≅ diuretic + propranolol or methyldopa

            Adverse Effects
    1.                                                           dose-
            CNS: Sedation, inability to concentrate, nightmares, dose-
            related psychotic depression – contraindicated in pre-
            e st g dep ess o .
            existing depression.

    2.      Unabated parasympathetic activity - nasal stuffiness,
            ↑gastric acid secretion (contraindicated in peptic ulcer),
            diarrhea and bradycardia

                   Central α2 agonists
Generic name Trade              Doses available
Clonidine         Catapress® Oral: 0.1, 0.2, 0.3mg
                             Transdermal patch: 0.1, 0.2, 0.3mg/24hrs
Methyldopa              -       Oral:250, 500mg
Guanabenz         Wytensin®     Oral: 4, 8mg
Guanfacine        Tenex®        Oral:1, 2mg

     Mechanism of action

Selective α2 agonists in the CNS:
↓ CNS sympathetic outflow – enhanced
parasympathetic activity - ↑vagal tone - ↓BP

↓HR, ↓CO, ↓ TPR, ↓plasma renin, blunted
baroreceptor reflexes.

↓ NE plasma levels directly ↓ TPR with ↓BP.

 Clonidine useful in pheochromocytoma diagnosis


D     f h i in thi l            f l     li it d b
Drug of choice i this class; usefulness limited by
adverse effects.

Chronic use results in Na+ and fluid retention (diuretic).

Metabolized to its active form (α-
methylnorepinephrine) in the brain

      ∝- Methyldopa

          t1/2: 2hrs; peak effect: ~6-8hrs; Duration of action:

          In elderly: ↓HR and ↓ stroke volume resulting in ↓
          CO, in young uncomplicated patient no such effect.

          Adverse effects:
            Sedation, l it d i ht          d     i
            S d ti lassitude, nightmares, depression,
            vertigo, galactorrhea (men & women).

   ↓ CO and ↓ TPR

   ↓ cardiac sympathetic tone leads to ↓ iontropy, ↓ chronotropy

   Adverse Effects:
  1. CNS – Sedation; avoid in depression
  2. Dry mouth

                    Not 1st line therapy



             Dose-                                    18-
             Dose-related withdrawal syndrome within 18-36 hrs;
             ↑sympathetic discharge leading to rebound hypertension
             or overshoot hypertension.

             Symptoms: headache, apprehension, tremors, abdominal
             pain, sweating, and tachycardia.

                      ACE Inhibitors

Generic name      Trade name(s)         Doses available
Enalapril         Vasotec®              Oral: 2.5, 5, 10, 20mg
Captopil          Capoten®              Oral: 12.5, 25, 50, 100mg
Lisinopril        Zestril®, Prinivil®    Oral: 2.5, 5, 10, 20, 40mg
Fosinopril        Monopril®              Oral:10, 20, 40mg
Benazepril        Lotensin®             Oral: 5, 10, 20, 40mg
Quinapril         Accupril®             Oral: 5, 10, 20, 40mg

Renin-Angiotensin-Aldosterone System
                                Angiotensin I
                                          Angiotensin Converting Enzyme
                                Angiotensin II

   ↑ Na+, H2O retention         Aldosterone               Vasoconstriction

     ↑ Blood volume             Facilitates NE transmission

           CO             X         ↑TPR

  ACE inhibitors block bradykinin degradation, stimulate PE2 & prostacyclin

         ACE Inhibitors

     As effective as diuretics and β-blockers

     Supervise 1st dose

      ↓TPR without reflex ↑CO, HR or inotrophy

     Fetotoxic (absolutely contraindicated in pregnacy)

     Initiate with very low dose with slow titration.

      Other Indicators

CHF (↓nonfatal and fatal events).

LVH (may prevent or partial regression).

Type 1 diabetic nephropathy

     Adverse Effects
   Acute hypotension (at onset, esp in severe Na & volume depletion)

   Ski     h(     ti       t
   Skin rash (sometimes transient)    i t)
   Cough (10% - 20%)

To a lesser extent (<1%):
   Hematologic toxicity: neutropenia, agranulocytosis
   Angioedema – more i Africans
   A i d                 in Af i
   Acute renal failure – esp. in unilateral/bilateral renal artery stenosis
   Proteinuria (captopril)
   Hyperkalemia – esp. in renal disease, DM, on NSAIDs, K+ supp. or K+-     K+-
   sparing diuretics

 Angiotensin II receptor antagonists

Generic name                   Trade name(s)          Doses available
Losartan                       Cozaar®                Oral: 25, 50, 100mg
Valsartan                      Diovan®                Oral: 40, 80, 160, 320mg
Candesartan                    Atacand®               Oral: 4, 8, 16, 32mg
Olmesartan                     Benicar®               Oral: 5, 10, 20, 40mg
Telmisartan                    Micardis®              Oral: 20, 40, 80mg
Irbesartan                     Avapro®                Oral: 75, 150, 300mg

            Mechanism of Action
                        Blockade of AgII receptors

           ↓ vasocontriction                 ↓Na+ retention
                                                                      Acute effect
                 ↓TPR                       ↓ Blood volume

                  ↓BP                            ↓CO

                Ag II                 Stimulation of arterial wall

                                          ↑wall to lumen ratio
                                                                     Long term effect
                Ag I                        (remodelling)

                                             ↑ vasoconstriction

                  No effect on bradykinin breakdown

   Angiotensin II receptor subtypes
             AT1 (site of action of ATII antagonists)
              –   Vasoconstriction
              –   Aldosterone release
              –   Sympathetic activation
              –   ADH release
              –   Constriction of efferent glomerular arterioles

             AT2 (beneficial effect not blocked)
              – Vasodilation

       AgII also produced by enzymic reactions of chymases

            Other Indications

      “ACE inhibitor without the cough”

      Heart failure

      Intolerance to other hypertensive drugs

All have similar antihypertensive efficacy with flat dose-response curve

              Adverse Effects

        Renal insufficiency (↓glomerular perfusion pressure)


    Caution: History of ACE inhibitor-induced angioedema

Generic name
                      Trade            Available doses
Chlorothiazide        Diuril®          Oral: 250, 500; 250mg/mL oral suspension

Hydrochlorothiazide   Hydrodiuril®     Oral: 25, 50, 100mg tabs; 12.5mg capsules
                                       Parenteral: 10mg/mLsoln
Chlorthalidone        Thalitone®       Oral: 250, 500 mg; 250 mg/5mL oral
Indapamide            Lozol®, others   Oral: 1.25, 2.5mg
Metolazone            Zaroxolyn®       Oral: 0.5mg
Furosemide            Lasix®           Oral: 20, 40, 80 mg; Parenteral: 10mg/mL

Bumetamide            Bumex®           Oral: 0.5, 1, 2 mg; Parenteral: 0.5mg/2mL

Torsemide             Demadex®         Oral: 5, 10, 15, 20mg; Parenteral: 10mg/mL

Ethacrynic Acid       Edecrin®         Oral: 25, 50mg; Parenteral: 50mg/mL
Spironolactone        Aldactone®       Oral: 25, 50, 100mg
Eplerenone            Inspra®          Oral: 25, 50mg
Amiloride             Midamor ®        Oral: 5mg
Triamterene           Dyrenium®        Oral: 50, 100mg

       Diuretics – Thiazides (1st line)
 Acute effect                    Block renal tubule Na+-Cl- reabsorption

                         -ve effect
  ↑ angiotensin II                    ↑ urinary loss of Na+ and H2O

                                       ↓ extracellular volume
   ↑ renin release
                                                ↓CO                        ↓BP
Long term effect
  •CO returns to normal
  •Slight ↓ in body Na+                    ↓[Ca2+] in vascular smooth muscle cells
  •Opening of K+ channels                  ↓affinity of vascular smooth muscle cells
  (hyperpolarization)                       for vasoconstrictor hormones

           ↓BP                 ↓TPR               ↓ Contractility of vascular
                                                  smooth muscle cells

      Diuretics – Furosemide (not 1st line)

 Acute effect        Binds to Cl- binding site of Na+-K+-2 Cl- cotransporter in
                                   thick ascending loop of Henle
        ↑ Angiotensin II                   ↑ loss of Na+ and H2O

                                        ↓ Extracellular fluid volume

      ↑ Renin release
                                                ↓ CO               ↓BP
Long t
L          ff t
     term effect
 •CO returns to normal                        ↓ Contractility of VSMC
 •Slight ↓ in body Na+

                         ? ↓BP ?                       ↓TPR

     Loop Diuretic – Furosemide

        Resistant hypertension (not 1st line)

        Edema (renal impairment or volume overload)



                  Ca2+ channel blockers
Generic name         Trade         Doses available
Benzothiazepine      Cardizem®     Oral: 30, 60, 90, 120mg; sustained release: 60,
Diltiazem                          90, 120, 180, 240, 300, 360, 420mg.
                                   Parenteral: 5mg/mL soln
Diphenylalkylamine   Calan®,       Oral: 40, 80, 120mg; sustained release: 120,
Verapamil                          180, 240mg
                                   Parenteral: 2.5mg/mL soln
Dihydropyridine      Adalat® CC,   Oral: 10, 20mg. Extended release: 30, 60, 90mg
Nifedipine           Procardia®
Amlodipine           Norvasc®            2.5, 5,
                                   Oral: 2 5 5 10mg

Felodipine           Plendil®      Oral extended release: 2.5, 5, 10mg

Isradipine           DynaCirc®     Oral:2.5, 5mg; controlled release: 5, 10mg

Nicardipine          Cardene®      Oral:20, 30mg; sustained release: 30, 45, 60mg
                                   Parenteral: 2.5mg/mL soln
Nisoldipine          Sular®        Oral extended release: 10, 20, 30, 40mg

                   Mechanism of Action
           Dihydropyridines                   Verapamil, Diltiazem
        Nifedipine Amlodipine

        Block L-type Ca2+ channels            Block L-type Ca2+ channels
         in arterial smooth muscle               in SA and AV node

                ↓ TPR                                ↓ or abolishes
                                                   reflex tachycardia

                   ↓ BP
              reflex tachycardia

  Inhibit influx of Ca++ ions thru’ voltage-gated channels

              Relative efficacy

    Drug          Vasodilation -ve inotropy   Automaticity         AV
                   (coronary                   (SA node)       conduction
                     flow)                    suppression      suppression
Diltiazem               3            2              5                   4

Nifedipine              5            1              1                   0

Verapamil               4            4              5                   5

Relative cardiovascular effect: 0=no effect, 5=maximum effect


Mild to moderate HTN associated with exercise-
induced, variant and unstable angina.

MI (ACE inhibitors>protective than dihydropyridines)

Antiarrhythmic (diltiazem and verapamil for
(supraventricular tachycardia, atrial fibrillation and
atrial flutter).

Not clinically superior to diuretics or β-blockers,
           usually 2nd & 3rd line therapy.

    Adverse Effects

  Vasodilatory-related (more with
  dihydropyridines): dizziness, flushing,
  headache, peripheral edema

  Gingival hyperplasia

  Mood swings & fatigue

  Verapamil causes constipation (7%) and
  contraindicated in CHF

 Oral and parenteral vasodilators
Generic name              Trade name(s)    Doses available

Hydralazine               Apresoline®      Oral: 10, 25, 50, 100mg
                                           Parenteral: 20mg/mL soln
Nitroprusside             Nitropress®      Parenteral: 50mg/vial

Minoxidil                 Loniten®         Oral: 2.5, 10mg
                                           Topical (Rogaine®, etc): 2% soln
Diazoxide                 Hyperstat® IV    Oral: 50mg capsule
                                           Parenteral: 15mg/mL
Fenoldopam                Corlopam®        Parenteral: 10mg/mL soln

            Well absorbed orally, short t1/2 (1 hr), peak effect (1/2 hr to
            2 hrs) & duration of action (12hr)

            Bioavailability determined by acetylator status:
            16% in ‘fast’ and 35% in ‘slow’ acetylators.

            Adverse effects limit use. Reserved for refractory severe
            hypertension used concomitantly with diuretics and β-
             yp                             y
            blockers (never as monotherapy).

            Used occasionally with isosorbide dinitrate in CHF.

                 Contraindicated in CAD and > 40years


   ect e a at o o a te es ( ot ve s), c
Direct relaxation of arteries (not veins), cAMP

Vasodilatation causes baroreceptor-mediated reflex,
sympathetic stimulation → tachycardia → ↑ CO; ↑
renin release → ↑ Na+ and H2O retention.

↑CO and fluid retention cause tachyphylaxis, unless
used in combination with β-blockers (↓reflex
tachycardia) and diuretics (↓fluid retention).

 Hydralazine: Adverse Effects

Direct extension of pharmacological activity:
headache, nausea, flushing, dizziness, hypotension,
palpitation, tachycardia, angina pectoris, MI

Immunological reactions (unknown mechanism):
– Serum sickness, hemolytic anemia, vasculitis, rapidly
  progressing glomerulonephritis
  10-                            dose-
– 10-20%incidence of reversible dose-related lupus
  erythematosus-like syndrome – high dose or after
  >6mth chronic use. (Use <200mg daily)
  Effect > in females and ‘slow acetylators’.
      Limited usefulness in hypertension

Direct relaxation of arteries (not veins).

↑blood flow to skin, skeletal muscles, GI
tract, heart.

Reflex ↑CO, renal vasodilatation and
↑renin secretion


  p     y       y
> potency than hydralazine

Well absorbed orally, short t1/2:3-4 hrs, duration of action:

NEVER as monotherapy, use with β-blockers and
          ( p           )
diuretics (loop diuretic).

Reserved for refractory severe hypertension.

Minoxidil – Adverse Effects

  More dramatic ↑fluid retention than hydralazine (not
  ↑renin and aldosterone secretion related). ↓ renal
  perfusion pressure and reflex stimulation of renal tubular

  Headache, sweating

  Used topically to treat of male-pattern baldness.

Sodium nitroprusside
  Given by iv continuous infusion. Onset: 30sec; peak
  effect: 2 mins.

  Metabolized to NO and cyanide.
 1. NO causes vasodilatation.
 2. Cyanide is poisonous, and further metabolized to

  Very potent vasodilator of both arteries and veins

  Drug of choice in hypertension emergencies

 Sodium nitroprusside

M d ↑HR and ↓myocardial O2 d
Modest    d        di l         d

Other indications:
– Acute aortic dissection (propranolol given first
  to prevent reflex sympathetic activation).
– In CHF to ↑CO
– In acute MI to ↓myocardial O2 demand

Sodium Nitroprusside:
Adverse Effects
Cyanide and thiocyanate poisoning:
 – Anorexia, nausea, fatigue, disorientation, toxic
 Closely monitor BP and plasma thiocyanate (<0.1μg/mL).
 Antidote: Infusion of sodium thiosulphate → thiocyanate
 ↑risk of poisoning in impaired renal function

Worsens arterial hypoxemia in COPD

Abrupt cessation after short-term use causes rebound HTN.

   Prescribed Antihypertensive Drugs in Trinidad (n=442)
Drug Class/Generic Drug name                 All HTN N (%)               HTN alone N (%)      HTN with DM       N (%)
ACE Inhibitors (ACEI)                          281 (63.6)                   113 (58.9)             168 (67.2)
Enalapril                                         247                          95                     152
Lisinopril                                         30                          15                      15
Fosinopril                                          2                           1                       1
Captopril                                           2                           2                       0
β-blockers (BB)                                129 (29.2)                   65 (33.9)              64 (25.6)
Atenolol                                          117                          61                     56
Propranolol                                        9                            4                      5
Bisoprolol                                         3                            1                      2
Diuretics                                      114 (25.8)                   66 (34.4)              48 (19.2)
Thiazide (bendrofluazide)                         89                           50                     39
Furosemide                                        25                           16                      9
Calcium channel blockers (CCB)                  53 (12.0)                   23 (12.0)              30 (12.0)
Nifedipine                                         45                          22                     23
Amlodipine                                          5                           0                      5
Verapamil                                           3                           1                      2
α-blockers                                       3 (0.7)                     1 (0.5)                 2 (0.8)
Terazosin                                           1                           1                       0
Doxasosin                                           2                           0                       2
Angiotensin receptor blockers (ARB)             10 (2.3)                     5 (2.6)                 5 (2.0)
Valsartan                                          9                            5                       4
Presartan                                          1                            0                       1
Other drugs                                     27 (6.1)                     18 (9.4)                9 (3.6)
Methydopa                                         23                           16                       7
Reserpine                                          4                            2                       2

     Antihypertensive drug therapy in Trinidadian patients
     with complete accessible drug records (n=442)

             Antihypertensive drug therapy            All HTN patients           HTN alone      HTN with DM
                                                           N (%)                  N (%)           N (%)

             No drug therapy                                 26 (5.9)               8 (4.2)        18 (7.2)

             Monotherapy                                    242 (54.8)            86 (44.8)       156 (62.4)

             Dual drug therapy                              121 (27.3)            62 (32.3)       59 (23.6)

             Triple drug therapy                            45 (10.2)             30 (15.6)        15 (6.0)

             Quadruple drug therapy                          8 (1.8)                6 (3.1)        2 (0.8)

             TOTAL                                             442                      192          250

                   β-blockers                 α1-blockers

                   ↑β1 receptor                 ↑ CO
↑sympathetic     cardiac activation
          y                                                   ↑ BP
                    ↑α1 receptor               ↑ TPR
               smooth muscle activation

               Ca2+-channel                            ACE inhibitors
 ↓ BP            blockers          Vasodilators

↓ Renal flow           ↑ renin            ↑ Angiotensin II
                                                        AgII receptor
                      ↑Aldosterone                        blockers

   ↓GFR           ↑Na+, H2O retention     ↑ Blood volume



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